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What Are the Best Peptides for Pain Management?

peptides for pain

Approximately 60 million people worldwide endure chronic pain. 

These folks suffer from mild to severe pain that does not easily go away.

However, despite the government adopting the 1961 Single Convention on Narcotic Drugs for pain relief, millions of people worldwide still suffer from severe pain. 

It’s no wonder why the International Pain Society and Global Health Community considered failure to treat pain as an unethical practice. 

“Failure to treat pain is viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.”

Since then, pain management has become a basic human right, compelling governments worldwide to provide pain treatment to people as part of their obligations under the right to health. 

“Failure to take reasonable steps to ensure that people who suffer pain have access to adequate pain treatment may result in the violation of the obligation to protect against cruel, inhuman and degrading treatment.”

The problem is that traditional treatment options, such as opioids and over-the-counter anti-inflammatory drugs (NSAIDs), can only manage symptoms and do not address the root cause of the pain problem. 

That’s not to mention the unwanted undesirable effects that come with them. 

For example, NSAIDs can lead to life-threatening ulcers over time, while opioids can result in hallucinations, sleep apnea, hypotension, and paradoxical opioid-induced hyperalgesia (OIH). 

Fortunately, a new and promising therapeutic approach to pain management has been developed with little to no adverse effects on your health.

We’re talking about the use of peptides in pain management. 

Peptide Therapy: A Promising Alternative to Traditional Painkillers

peptides for pain

Unlike traditional painkillers that entail numerous drawbacks, peptides for pain are considered therapeutic agents that can help sharpshoot specific pain receptors with fewer side effects and without the potential for addiction.

“In the past, first-line treatment options for chronic pain were touted as top-of-the-line analgesics, but as time progressed, the veneer began to peel and the less-than-desirable consequences of their use became more and more obvious,” explained researcher Dr. Rasheen Powell in an exclusive interview with Drug Target Review.

Two common types of pain people experience are caused by inflammation and neuropathy.

Inflammatory pain

Inflammatory pain occurs in response to tissue damage and inflammation, such as arthritis and myositis.

When you have chronic inflammation, you can experience joint and muscle pain, stiffness, and tendonitis, and the inflamed area is sensitive to touch.

Neuropathic pain

Neuropathic pain occurs because of a damaged central nervous system. Over time, the pain feels like an electric burning sensation, making you weak.

Neuropathic pain can be hard to manage and may significantly affect your quality of life.

Fortunately, peptides can help address the root causes of both inflammatory and neuropathic pain.

Below are the five best peptides for pain that you can use to find relief.

5 Best Peptides for Pain Relief

peptides for pain


BPC-157 is a synthetic peptide consisting of a sequence of 15 amino acids.

It comes from the “body protecting compound” (BPC), a gastroprotective protein that is isolated from human gastric juice.

Growing studies have shown that BPC-157 is one of the best peptides for pain, helping to reduce joint pain, heal skin burns, improve joint mobility, and boost recovery from musculotendinous injuries. 

In one study published in the Journal of Cell and Tissue Research, participants who took BPC-157 peptides reported a reduction in their joint pain. Their mobility improved, and they were able to stand and walk without feeling as much pain. 

Currently, all studies investigating BPC-157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic, and for a plethora of soft tissues.

BPC-157 can also speed up recovery from injuries. 

It’s been shown that the peptide can help speed up recovery after an injury to the Achilles tendon caused by ligament and muscle tears and nerve damage, after just two weeks of using peptide therapy.

Currently, in clinical trials for inflammatory bowel disease, it ameliorates internal and external wound healing. 

In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied 30 minutes after surgery, the last application at 24 hours before autopsy. 

Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC-157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young’s modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity.

It can also help accelerate bone health, especially in people with osteoporosis. 

In fact, rabbits who were given peptides had significantly improved pain levels caused by osteoperiosteal bone defects after 6 weeks of using peptide injections for pain compared to the control group. 

Rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). 

As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. 

Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. 

For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 μg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. 

How does BPC-157 accomplish this?

In three ways.

First, using BPC-157 can speed up the growth of fibroblasts and increase rates of oxidative resistance. It also helps in F-actin formation, which is involved in the spreading of fibroblasts. 

Fibroblasts are cells found in connective tissues, which are essential in collagen production and reformation, especially post-surgery.

With this, BPC-157 can help promote ligament and tendon health.

Experimentally, it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC-157 was examined.

Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. 

Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC-157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H(2)O(2) stress. 

BPC-157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner, as revealed by transwell filter migration assay. 

BPC-157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts.

Second, BPC-157 has antioxidant properties, which can protect your body against oxidative stress that may contribute to inflammation and tissue damage.

In fact, in several animal studies, BPC-157 was believed to regulate inflammatory mediator levels, such as cytokines and prostaglandins in the body. 

BPC-157 counteracts tumor cachexia and muscle wasting and increases pro-inflammatory/procachectic cytokines, such as interleukin-6 and tumor necrosis factor-α. It also significantly corrects deranged muscle proliferation and myogenesis through changes in the expression of FoxO3a, p-AKT, p-mTOR, and p-GSK-3β (mitigating cancer cachexia).

As a result, the peptide leads to reduced pain and swelling while promoting tissue repair and recovery.

Third, BPC-157 can also help increase blood flow by improving angiogenesis.

Angiogenesis is the process by which your body creates new blood vessels while improving blood flow in wounded areas of the body in order to help with pain and recovery. 

Our previous study reveals that BPC-157 can markedly promote the expression of vascular endothelial growth factor VEGF receptor 2 (VEGFR2) and angiogenesis in ischemic hind limb. 

BPC-157 accelerated the blood flow recovery in ischemic hind limb simply through angiogenesis since there was no significant difference in the blood flow or pressure in tails between the control and BPC-157 groups. 

Not only that, but BPC-157 can also help protect your gut from damage caused by taking NSAIDs. 

While NSAIDs act great as painkillers, they can be toxic to the gut over time.

Taking excessively high doses can result in ulcers, blurred vision, vomiting, or worse, leading to organ damage.

Fortunately, BPC-157 can help reverse the damage caused by mediated lesions in the gastrointestinal tract, liver, and brain.

It’s no wonder that researchers call it an antidote to nonsteroidal anti-inflammatory drugs (NSAIDs).

It can also counteract and prevent damaging symptoms, like bleeding, caused by taking ibuprofen and aspirin.

BPC-157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis))

In a nutshell, BPC-157 works by enhancing the body’s natural healing processes, thereby speeding up the rate of recovery from injury.

It’s definitely one of the best peptides for suppressing inflammation.


ARA-290, or Cibinetide, is a synthetic peptide that consists of 11 amino acids. 

This peptide, developed by Araim Pharmaceuticals, is derived from the helix beta domain of erythropoietin (EPO).

Erythropoietin (EPO) is a glycoprotein hormone, naturally produced by the peritubular cells of the kidney, which stimulates red blood cell production.

EPO production also occurs in the spleen, liver, bone marrow, lung, and brain in small quantities.”

Studies have shown that the administration of recombinant human EPO (rhEPO) helps reduce inflammation and activate the healing process in pre-clinical models and patients.

This means ARA-290 can help prevent tissue injury, reduce inflammation, and activate healing.

This peptide is believed to lessen the severity of neuropathic pain and reduce inflammation by down regulating inflammatory pathways.

This is done by blocking the activity of the TRPV1 channel, which is responsible for the sensation of pain and heat – both common symptoms of neuropathic disorders. 

In this study, we were particularly interested in whether ARA-290 could directly target peripheral nociceptors by blocking or influencing receptors in pain sensation.

Using calcium imaging, cell culture, and behavioral tests, we demonstrated that ARA-290 was able to specifically inhibit TRPV1 channel activity and relieve the mechanical hypersensitivity induced by capsaicin.”

Researchers also believe ARA-290 can help increase the number of tiny nerve fibers, reducing the intensity of pain.

You see, diabetes can damage the lightly myelinated or small unmyelinated fibers of the autonomic nervous and peripheral sensory systems.

This disorder is called small fiber neuropathy (SFN). 

This process is characterized by autonomic dysfunction and neuropathic pain.

Diabetic painful neuropathy can be regulated through an inflammatory chemokine pathway and using gene transfer of soluble TNF receptors to minimize inflammation. 

ARA-290 has been shown in pre-clinical models to improve peripheral neuropathic pain by stimulating nerve fiber regrowth from damaged axons and reducing inflammation.

This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL [small nerve fiber loss] and neuropathic pain assessed the effect of cibinetide on the corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity.

“…Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group.” 

ARA-290 can also block the activation of macrophages. 

Macrophages, when exposed to inflammatory stimuli, secrete cytokines such as IL-1, IL-6, IL-8, IL-12, and necrosis factor (TNF), which are involved in the process of pathological pain.

Therefore, you can use peptide ARA-290 to deal with your inflammatory and neuropathic pain. 

Use it consistently for 30 days to decrease the reactivity of nerve cells and feel no more pain in about 6 months. 


SEMAX® is a neuroactive peptide developed from a short fragment of ACTH, Pro8-Gly9-Pro10 ACTH(4-10). 

ACTH is short for “adrenocorticotropic hormone,” and it plays a huge role in controlling our stress levels.

This peptide is made in the corticotroph cells of the anterior pituitary gland.

It is secreted in several intermittent pulses during the day into the bloodstream and transported around the body. 

Like cortisol, ACTH levels are highest when we wake up in the morning.

It falls throughout the day and is at its lowest during sleep. 

This process is called the diurnal (circadian) rhythm. 

Once in the adrenal glands, ACTH binds onto receptors, causing the adrenal glands to produce more cortisol in the blood. 

You see, cortisol helps boost the immune system by suppressing inflammation.

However, if you have too much cortisol in your blood, your body can get used to it, resulting in inflammation and a weakened immune system. 

Fortunately, Semax can help lower cortisol levels to help maintain healthy inflammation.

Semax can also boost brain-derived neurotrophic factor (BDNF) levels. 

BDNF is an active protein that helps stimulate and support the development, survival, and functions of neurons.

It also acts as a pain mediator and modulator. 

This means it can contribute as normal and regulate pain at the same time by performing its biological functions through two receptors: p75 neurotrophin (pan‐selective p75 neurotrophin receptor) and the TrkB receptor (tropomyosin receptor kinase B or tyrosine receptor kinase B).

BDNF is released in response to peripheral inflammation and is known as a nociceptive modulator for both pain perception and sensitization at both spinal and supraspinal levels. 

p75 is a low-affinity receptor, while the tropomyosin receptor kinase B (TrkB) receptor is a high-affinity receptor and is upregulated in chronic pain states. 

Semax also inhibits the breakdown of enkephalins.

Enkephalins are chemical compounds that can help with pain reduction and inflammation, immune cell activity, and cancer cell growth.

It works by binding with the body’s natural opioid receptors. 

“… we assumed that one of the mechanisms of action of Semax and Selank is related to their effect on the endogenous opioid system, which can be due to both direct interaction of the peptides with the opioid receptors and their influence on the activity of the enzymes of the endogenous opioids processing or degradation.

It was found that both Semax and Selank considerably decelerate the [Leu]enkephalin degradation by the human serum enzymes.”

It also boosts enkephalin production, which can help minimize pain sensation and severity.

Semax pain management properties work regardless of how the pain is inflicted, as proven in a rat study.

When studying the analgetic effects of Semax, we used different types of painful irritants: thermal (the hot plate and tail flick tests), mechanical (hind leg squeezing), and chemical (writhing).

The increase in pain threshold in different tests indicates that the analgetic effects of Semax do not depend on the type of painful irritant used.

Thus, the results of our experiments demonstrated that Semax, as well as ACTH, MSH, and their fragments and synthetic analogs, is an analgesic.

Based on analysis of these results and published data [2–4], we may assume that the analgetic effects of Semax and other melanocortins are related to supraspinal mechanisms of the control of the sensitivity to pain.”

This shows Semax’s pain-relieving properties can help people with neuropathy and inflammation problems. 


Researchers at the University at Buffalo discovered a novel, durable peptide that can help treat inflammatory pain

This research, led by Arin Bhattacharjee, PhD, associate professor of pharmacology and toxicology at the Jacobs School, originally investigated the origins of pain sensation. 

However, their findings paved the way for the discovery of a new peptide that can help with pain relief in a much better way than opioids. 

According to Bhattacharjee, this peptide can penetrate nerve endings, providing long-lasting relief after just a single administration.

The researchers looked into the calcitonin gene-related peptide (CGRP), a specific type of neuron that contains pain neurons. 

They discovered that this peptide can express AP2A2, a specific endocytosis subunit, unlike other sensory neurons. 

This led them to dig deeper and find solutions to help minimize chronic pain without the side effects.

They started by looking at pain neurons. 

Pain neurons help send information to the brain, telling it where the injury is located and how severe the injury is. 

“At the molecular level, our research is helping unravel how tissue injury signals to pain-sensing neurons. If we can understand this at the molecular and cellular level, we can then identify novel pain-killing targets,” said senior author and Associate Professor Arin Bhattacharjee. 

Using animal studies, biochemical approaches, and electrophysiology, their team identified that endocytosis in neurons plays an important role in the development and maintenance of inflammatory pain.

 “We wanted to make use of complementary techniques to validate the voracity of our observations,” Powell elaborated.

“So, we began with an in vivo genetic knockdown technique to knockdown a nociceptor sub-type specific isoform of the alpha-AP2 subunit.”

From this, they created CGRP to prevent endocytosis and minimize the hyperactivity of pain neurons, resulting in minimal pain reception.

“This novel peptide molecule is a lipidated endocytic dileucine sequence found in the human CD4 protein known to bind to the AP2 complex at the sigma/alpha-subunit interface,” explained Powell. 

They added an N-terminal myristoyl group to modify the endocytic motif and increase its lipophilicity.

This enables the peptide to embed into the cell membrane and penetrate the cell through a ‘flip-flop’ mechanism.

“By adding this myristoyl group, we have limited the effects of the peptide to only interactions at the inner leaflet of the cell membrane, while also prolonging its duration of action by creating a replenishable pool of peptide on the outer leaflet of the cell membrane,” Powell added.

As a result, using this peptide can disrupt endocytosis when applied locally at the pain nerve endings.

For example, anesthetics not only block the pain but also block all sensory neurons. 

The result?

The patient feels numb for only a short while and only requires painkillers after the anesthesia wears off. 

However, this is not the case with CGRP.

When locally applied, CGRP can decrease pain behaviors for up to six days. 

“Our novel technology seems to solve this problem by getting into nerve endings and staying there. The result is a long-lasting reduction in pain behavior.” As the authors noted, “…we have demonstrated locally administered lipidated peptidomimetics are able to produce specific and long-lasting reductions in pain-like behaviors.”

Ultimately, CGRP has no adverse side effects compared to NSAIDs or the risk of drowsiness and addiction like opioids.

It’s no wonder why it’s considered one of the best peptides for pain available to date.


TB-500 is a synthetic version of Thymosin beta 4, a naturally occurring peptide, with more enhanced attributes.

Studies have shown that this peptide helps in rapid tissue repair and healing wounds and injuries.

It stimulates new blood vessel formation, facilitates tissue regeneration, and minimizes inflammation. 

This is best for athletes, as they are prone to chronic or acute musculoskeletal issues, as well as micro-tears, strains and sprains. 

Additionally, TB500 can improve your flexibility while reducing inflammation. 

It works by binding with actin, a cellular building block that is important in wound healing and damaged tissue repair. 

It inhibits the polymerization of globular actin (G-actin) into filamentous actin (F-actin), resulting in upregulated G-actin levels

This binding happens via Ac-LKKTETQ, a central actin-binding domain. 

The prevention of F-actin polymerization changes the cellular cytoskeleton

This affects the cell’s ability to move and change shape, which is crucial in wound healing, tissue regeneration, and cancer metastasis. 

Recently, beta 4 was found to bind actin in human platelet extracts and to inhibit actin polymerization in vitro, raising the possibility that it may be a physiological regulator of actin assembly. 

To examine this potential function, we have increased the cellular beta 4 concentration by microinjecting synthetic beta 4 into living epithelial cells and fibroblasts. 

The injection induced a diminution of stress fibers and a dose-dependent depolymerization of actin filaments, as indicated by quantitative image analysis of phalloidin binding. 

Our results show that beta 4 is a potent regulator of actin assembly in living cells.

TB-500 can also be found outside of cells in wound fluid or blood plasma.

In a study published in The International Journal of Biochemistry & Cell Biology, the application of extracellular TB-500 can help regulate angiogenesis and cell motility. 

It works by interacting with cell surface-located ATP synthase enzymes, which play a crucial role in the energy production of cells.

It can also help minimize inflammation through increasing microRNA-146a (miR-146a) expression while decreasing L-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression.


peptides for pain

Using peptide injections for pain is a promising approach to pain management.

They target specific biological pathways involved in tissue repair, leading to faster and more efficient healing of injured tissue.

Although you might experience initial side effects such as nausea and or mild headaches with peptide therapy, it is still considered safer compared to opioids, anabolic steroids, and NSAIDs.

To help speed up your recovery, maintain an active lifestyle and consume a non-inflammatory insulin controlled diet with healthy levels of protein and essential fatty acids.

If you’re in search of high-quality peptides for pain that have been clinically tested and have proven effective ingredients to manage inflammatory and neuropathic pain…

We recommend Limitless Life Nootropics, as they have some of the best formulations of peptides for pain management in the market. 

That’s not to mention Limitless offers the BEST deals on both price and peptide purity.

Use code JAY15 at the checkout cart for 15% off!


But before you start injecting them into your body recklessly, make sure you first read the Top 10 Mistakes People Make When Starting Therapeutic Peptides FREE PDF!

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